| Summary: | Amphibians are widely known as a prolific source of bioactive metabolites. In this work, we isolated and characterized compounds with antiparasitic activity from the oocytes of the toad <i>Rhinella alata</i> collected in Panama. Bio-guided isolation and structural elucidation were carried out using chromatographic and spectroscopic techniques, respectively. The organic extract was subjected to solid phase extraction followed by HPLC purification of the fraction with in vitro activity against <i>Trypanosoma cruzi</i> trypomastigotes. Seven steroids (<b>1</b>–<b>7</b>) of the bufadienolide family were isolated, and their structures were determined using NMR and MS analyses; of these 19-formyl-dyscinobufotalin, (<b>3</b>) is reported as a new natural product. Compounds <b>1</b> and <b>3</b>–<b>7</b> resulted in a good anti-trypanosomal activity profile. Among these, 16β-hydroxyl-hellebrigenin (<b>1</b>) and bufalin (<b>7</b>) showed significant selectivity values of >5 and 2.69, respectively, while the positive control benznidazole showed a selectivity of 18.81. Furthermore, molecular docking analysis showed compounds <b>1</b>, <b>3</b> and <b>7</b> interact through H-bonds with the amino acid residues GLN-19, ASP-158, HIS-159 and TRP-177 from cruzipain at the catalytic site. Given the lack of therapeutic options to treat American trypanosomiasis, this work can serve as the basis for further studies that aim for the development of bufadienolides or their derivatives as drugs against Chagas disease.
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